'Nightmare Bacteria' Defy Even Last-Ditch Drugs

Now for nightmare bacteria. They defy all our antibiotics, even our latest drugs. This week the Centers for Disease Control and Prevention announced that strains of these completely drug-resistant bacteria have quadrupled in the last decade or so, and the bugs have been lurking around in hospitals, hundreds of hospitals around the nation.

In 2011 they even snuck into the National Institutes of Health's own clinical center. Is there anything we can do to stop the march of these deadly bacteria? Why are we seeing so many antibiotic-resistant bacteria today? Are we overusing, abusing antibiotics? Is that playing a real-world game of survival of the fittest? Are we doing that with these bugs?

And don't forget, it's not just we humans who use antibiotics. We pour four times as many antibiotics, that's nearly 30 million pounds of drugs, into our livestock. Much of that is just to fatten them up, not to fight infections, according to one of my next guests. Is that breeding even more resistance?

And as we run out of antibiotics, are there any new tactics we could use against the bugs? How about attacking them with viruses, phage? There must be a phage out there to kill those things, right? Well, here to answer some of those questions are my guests.

Dr. Tara Palmore is a deputy hospital epidemiologist at the NIH Clinical Center at NIH in Bethesda. She joins us from NPR in Washington. Welcome to SCIENCE FRIDAY, Dr. Palmore.

FLATOW: Dr. Palmore, tell us about the life of this bacterium. What makes it so strong that it can fight off everything that we throw at it?

PALMORE: These bacteria carry special resistance genes on a plasmid - a plasmid is a circle of DNA - that can be transmitted from one bacteria to another. These bacteria carry on their plasmids a gene that confers resistance to the most important and useful antibiotics that we have for that class of bacteria.

FLATOW: Let me - I'll ask Dr. Spellberg to jump in, too. Where did they get to be so strong? How did they get to be so strong?

SPELLBERG: Well, you know, there's a bunch of different really bad bugs out there. If we're focusing on the recent reports from the Centers for Disease Control and Prevention, this carbapenem-resistant Enterobacteriaceae, or CRE, it is the result of acquisition of a number of resistance genes. So they tend to be resistant to almost every antibiotic.

And the more - you know, resistance is the natural out product of us using antibiotics. When we use antibiotics, we kill off the susceptible bacteria, and we leave behind the bacteria that were already resistant, and now they can grow and replicate and spread and share their resistance genes.

FLATOW: But don't these bacteria, can't they live harmlessly inside of us and we now know them?

SPELLBERG: Indeed. In fact there are 10 times more bacteria on and in our bodies than there are human cells in our bodies. There's estimated to be about 100 trillion bacteria on and in us, the vast majority in our gut, compared to 10 trillion human cells. And those bacteria live on and in us normally, and in fact we need them for our health.

FLATOW: So these nightmare bacteria could be living in our gut just leaving us alone. What happens to them that they become toxic?

SPELLBERG: They when they're in our gut are doing what they have evolved to do, and we've co-evolved with them, which is to co-exist. When they get into the wrong place, all of a sudden our body reacts very violently to them. So again if we're focusing on the CRE family of bacteria, usually this happens to patients who have been exposed to medical care either in the hospital or a skilled nursing facility, and it's because as part of medical care, we put plastic catheters into people's.

We put plastic catheters into bladders. If people are having trouble breathing, we put them on a mechanical ventilator, and a plastic tube goes in their throat, down their lungs. And so we're breaking these anatomical barriers, and it allows bacteria that normally can't get into these sites to slip in there and cause problems.

FLATOW: Dr. Palmore, you were there when it happened at NIH?

PALMORE: Yes, that's right. Our cluster of CRE bacteria began in summer of 2011. And it began with a patient who came in with the bacteria, who was a carrier of the bacteria, which means as Dr. Spellberg mentioned that the bacteria were essentially living peacefully in that patient. But even when the bacteria are living peacefully, they are still transmissible.

So what happened despite our putting the patient in isolation is that we had transmission of the bacteria to other patients. And in total the cluster lasted from the summer of 2011 until the summer of 2012, resulted in nine patients with bloodstream infections and 10 patients who just became carriers.

FLATOW: So once that bacteria that normally lives harmlessly in your guts gets into a place it shouldn't be, into your blood, it could kill you 50 percent of the time.

PALMORE: At least 50 percent of the time. In fact several of the patients in our cluster died. And they died with bacteria that were resistant to all antibiotics. The patients in our hospital are highly immuno-compromised. They come to NIH for rare or extremely difficult to treat diseases. And so they were already quite ill when they acquired the bacteria.

And when the bacteria went into their bloodstreams, it turned out to be lethal in a number of cases.

FLATOW: All right, we're going to take a short break and talk about some creative ways to fight these killer bacteria, the CRE bacteria. If the antibiotics that we have don't work, what other ways can we fight them? Our number, 1-800-989-8255. We'll come back and talk more with Tara Palmore and Dr. Brad Spellberg. Dr. Palmore and Spellberg will be back with us when we get back after this break. So don't go away; we'll be right back.

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FLATOW: This is SCIENCE FRIDAY. I'm Ira Flatow. We're talking this hour about what the CDC calls nightmare bacteria, superbugs that can dodge even our last-ditch antibiotic weapons. Can we find some other way to attack them? I'm talking with Dr. Tara Palmore, she is deputy hospital epidemiologist at NIH's clinical center, that's at the NIH in Bethesda; Dr. Brad Spellberg, infectious disease specialist at L.A. Biomedical Research Institute in the Harbor-UCLA Medical Center in L.A. Our number, 1-800-989-8255.

Dr. Spellberg, what other options do we have other than just inventing more drugs? Because aren't the bacteria going to find a way to resist those also?

SPELLBERG: Well, that's true. Resistance is inevitable to anything we throw at these organisms. They're incredibly adaptable. But before we talk about others, other possibilities, we do need to underscore there is - there are very few interventions in all of medicine that have the power to reduce death like antibiotics do.

So when we talk about the need for alternatives, it's not to replace antibiotics, it's to supplement them and take some of the pressure off them so that they lost longer, and we don't have to use as much of them. But there are a variety of other options out there, including immune-enhancing strategies. You mentioned bacteria phages, that's, you know, certainly something that people are looking at.

FLATOW: Let's describe what that is. That's a virus that can attack the bacteria, and it occurs naturally in nature.

SPELLBERG: That's correct. So all bacteria can be attacked by specific viruses, just like humans can be attacked by viruses. And the United States and Europe played with bacteria phages as a treatment for infections in the pre-antibiotic era. In the late 1910s and in the early '20s, and there was published literature on this. And it really took off in Eastern Europe, which maintained a heavy presence of research in bacteria phages all the way through the 20th century.

The reality was that when compared to antibiotics, the power to reduce severity of infections wasn't quite as strong, and bacteria phages are certainly susceptible to resistance just like antibiotics are. So they kind of fell out of favor in the West, but in an era where we're running out of antibiotics, there is a renewed interest into exploring them as an adjunct to antibiotics.

FLATOW: And what about tweaking our own resistance to them, tweaking up our own ability to fight them off naturally? I mean, we've been living with these bacteria for lord knows how long, right? Shouldn't we have some natural immunity to them?

SPELLBERG: Well, there's good news and bad news there, right. You're absolutely right. So civilization, our species existed for probably 400,000 years or more before we knew what an antibiotic was, and civilization lasted 10,000 years before we knew what an antibiotic was. But there's no, absolutely no question that life spans, the average lifespan, was profoundly increased, and the incident of dying young of mundane infections profoundly decreased with the availability of antibiotics.

So it's not so much relying upon the natural immunity, we already have that. It's figuring out ways to stimulate new immunity or enhance immunity. And that type of research, which is done in my laboratory, that's what my laboratory focuses on, is of great interest, and we need to continue funding and continue to do that kind of research to try to develop something that is ready for primetime.

FLATOW: Dr. Palmore, would hand-washing even do anything to kill those nightmare bacteria if the antibiotics are not working?

PALMORE: Actually the bacteria are susceptible to hand-washing with soap and water. They're susceptible to hand gel that's alcohol-based. And in fact those are the primary methods of preventing transmission of all bacteria in the hospital. So what I usually tell people, many patients want to know how they can protect themselves from these bacteria, and I - my advice to them is make sure that every health care provider who comes into your room uses hand gel in front of you.

MEMO: Well, I'm an epidemiology student in Washington, D.C., and my question is: What are the greatest barriers to new antibiotic development today? I'll take my answer off the air.

FLATOW: All right, thanks for calling. Dr. Palmore, Spellberg?

SPELLBERG: Well, there's three barriers right now. We have a scientific challenge, and that is that we've had many antibiotics developed. So the low-hanging fruit have been plucked. So there are substantial scientific challenges of figuring out what's the next generation going to look like, trying to find a lead compound to go after.

There are regulatory barriers. For a variety of reasons, the Food and Drug Administration have been changing the rules on antibiotic clinical trials, which have made them much more expensive and risky than they used to be.

And then there is the economic barrier, which is that antibiotics are a very poor return on investment for companies. You take an antibiotic for seven days, and then you stop because it's cured the infection, or the patient dies if it's resistant. But companies make much more money selling a drug you take every day for the rest of your life, like a cholesterol-lowering drug or a blood pressure drug.

And when you factor those three things together, that accounts for the collapse of the antibiotic pipeline.

LUETTA: Well, thank you for taking my call. I just wanted to comment that you were originally going to talk about antibiotics in cattle feeding. I am a cattle feeder, and I know that the law says you cannot feed the antibiotics so many days before slaughter so that the antibiotic is cleared from the animal's body. I do use some occasionally for young animals, but as far as I know, there should be no antibiotics in the meat supply that our farmers raise. And thank you, I'll take my answer off the air.

FLATOW: OK, Dr. Spellberg?

SPELLBERG: Yeah, the issue is not whether there's antibiotics in the meat supply, the issue is whether there's antibiotic resistant bacteria in the food supply. And so remember, when you feed animals antibiotics, it changes their gut flora. The bacteria in their gut are now going to be resistant to those antibiotics.

You can take the antibiotics away. Those bacteria are still in there. And the other point I would make here is that I sometimes have people say I don't have to worry about that, I'm a vegetarian. Well, I've got news for you: Guess where the manure or the fertilizer comes to grow the crops? So antibiotic resistance absolutely puts resistant - or antibiotic use absolutely puts resistant bacteria potentially in the food chain.

FLATOW: If we don't have an antibiotic, we're basically going backwards in history, aren't we, to fight these new - the CRE bacteria?

SPELLBERG: Yeah, well, Dr. Palmore said, you know, at least a 50 percent chance of dying, and if you're resistant to everything, that goes up higher than that. And that is 1930 medicine. That's - you know, we need to remember the advances in medicine that were enabled by having effective antibiotics. Without effective antibiotics, there's no complicated surgery possible. The cancer chemotherapy is out the window; intensive care unit medications, care of premature neo-nates, organ transplants.

So yes, you would be setting medicine back 75 to 80 years.

FLATOW: Dr. Palmore?

PALMORE: Well, I think I totally agree, and I think that that is a reason right now to focus on how we can stop transmission in hospitals and health care facilities. I think the Centers for Disease Control made it clear that while these organisms have quadrupled in prevalence in health care facilities, we still have a chance to control them, which is something the nation of Israel did very effectively when they had a national outbreak about five years ago.

So I think focusing on implementing the guidelines for stopping transmission and putting the effort and resources both on a health care facility and on a regional level is really the key when we're talking about bacteria that can set us back like that.

FLATOW: Dr. Spellberg, if you say that industry is not concerned about developing new antibiotics, then who are we going to rely on?

SPELLBERG: Yeah, well I wouldn't phrase it that way. I think industry is concerned; they're just not interested because...

FLATOW: OK, (unintelligible).

SPELLBERG: No seriously because - companies have actively decided that we can't make a living doing this, and so...

FLATOW: Who are we going to depend on to do this? Because they make our drugs, don't they?

SPELLBERG: That's correct. I mean, you don't get drugs out of academic laboratories. The expertise and the capital are simply not available. So we need to change a variety of things. We need to make the regulatory landscape more amenable to develop. We need to move probably towards a different economic model, such as public-private partnerships.

And the government has been doing this. You know, the National Institutes of Health, and there's an agency in the Department of Health and Human Services called BARDA, have been funded to de-risk antibiotic development, take some of the upfront costs away, which then allows a company to come in and say OK my risk is lower, my upfront costs are lower, I can now tolerate a lower return on investment. And that may be the model that we have to move increasingly to in the future.

FLATOW: All right, I want to thank both of you for taking time to be with us today. Dr. Tara Palmore is deputy hospital epidemiologist at the NIH's clinical center, that's up at NIH in Bethesda. Dr. Brad Spellberg is an infectious disease specialist at the LA Biomedical Research Institute and the Harbor-UCLA Medical Center in LA. Thanks for joining us today.